Sign Up Now!
To sign up for our newsletter or print publications, please enter your contact information below.
First Name *
Last Name *
Email Address (Verify) *
We will request your mailing address on the next page.
We will request your mailing address on the next page.

AMG 701, a Bispecific T-Cell Engager Molecule, in RRMM: A Phase 1 First-in-Human Study

Conference Correspondent  - ASH Highlights

AMG 701 is an anti–B-cell maturation antigen (BCMA) half-life extended bispecific T-cell engager (BiTE) molecule in phase 1 development for relapsed/refractory multiple myeloma (RRMM). The primary objective of this phase 1 first-in-human study was to investigate the safety and tolerability of AMG 701 and determine a biologically active dose; secondary objectives included pharmacokinetic (PK) characterization, antimyeloma activity by International Myeloma Working Group criteria, and duration of response.

The study enrolled patients with multiple myeloma who either relapsed and/or were refractory or intolerant to ≥3 prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), or an anti-CD38 antibody. Intravenous AMG 701 infusions were administered weekly in 4-week cycles until progressive disease (PD), adverse event (AE), death, or consent withdrawal. In an attempt to prevent severe cytokine release syndrome (CRS), a step dose of 0.8 mg was administered before target doses ≥1.2 mg. By day 8, the target dose was reached. Doses of 5 μg to 45 μg were administered to 1 patient in each of the first 3 cohorts, doses of 0.14 mg to 1.2 mg were administered to 3 to 4 patients each in the next cohorts, and doses of 1.6 mg to 12 mg were administered to 3 to 10 patients each in subsequent cohorts.

Among 85 patients who received AMG 701, the median age was 64 years and the median time since diagnosis was 5.6 years; 25% had extramedullary disease, and 80% had received prior autologous stem-cell transplantation. The median number of prior regimens was 6, with 93% of patients having received a prior anti-CD38 antibody; 62% were triple refractory to a PI, an IMiD, and an anti-CD38 antibody. A total of 64 patients discontinued, primarily because of PD (80%), AEs (8%), and withdrawal of consent (6%). Median treatment duration was 7.6 weeks, and median follow-up was 6.5 months (for responders).

Anemia (42%), neutropenia (25%), and thrombocytopenia (21%) were the most common hematologic AEs, whereas CRS (65%), diarrhea (31%), hypophosphatemia (31%), fatigue (25%), and fever (25%) were the most common nonhematologic AEs. Most CRS events were grade 1/2 (n = 23 and n = 24, respectively), and grade 3 CRS events (n = 8) were reversible with corticosteroids and tocilizumab within a median of 2 days. Other dose-limiting toxicities were transient grade 3 atrial fibrillation, transient grade 3 acidosis, and grade 4 thrombocytopenia (1 each). Thirty-two patients (38%) experienced serious AEs, including infections (n = 14), CRS (n = 8), and asymptomatic pancreatic enzyme increase (n = 3). Four deaths occurred, but none was considered related to the study drug. Reversible treatment-related neurotoxicity occurred in 6 patients, lasted a median of 1 day, and was associated with CRS in 4 of these 6 patients.

An overall response rate (ORR) of 26% (21/82 evaluable patients) was observed, along with a rate of very good partial response or better (≥VGPR) of 17% (14/82). In the most recent evaluable cohort (n = 6), ORR was 83%; notably, 4 of 5 of these responders were triple refractory and 1 patient experienced grade 3 CRS. Overall, the following responses were observed: stringent complete response (CR), 5 (3 minimal residual disease [MRD] negative, 2 currently MRD undetermined); MRD-negative CR, 3; VGPR, 6; partial response, 7. The median time to response was 1.0 month, time to best response was 2.8 months, and interim median response duration was 5.6 months, with responses ongoing in 17/21 patients when last assessed, including a single patient who showed response at 22 months. A favorable PK profile was observed.

Results from this study of AMG 701 showed acceptable safety, promising efficacy, and a favorable PK profile in heavily pretreated patients with RRMM, thereby supporting ongoing evaluation and further clinical development of this agent.


Reference

Abstract 181. ASH 2020. December 5, 2020. A Phase 1 First in Human (FIH) Study of AMG 701, an Anti-B-Cell Maturation Antigen (BCMA) Half-Life Extended (HLE) BiTE® (bispecific T-cell engager) Molecule, in Relapsed/Refractory (RR) Multiple Myeloma (MM).

Related Items
Pevonedistat plus Azacitidine Improves Outcomes versus Azacitidine Monotherapy in High-Risk MDS
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Myelodysplastic Syndromes
Ruxolitinib in Graft-versus-Host Disease: Practice-Changing Results
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Graft-versus-Host-Disease
Step-Up Glofitamab Dosing Induces High Response Rates in Relapsed or Refractory Non-Hodgkin Lymphoma
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Clinical Trials, Lymphoma
ZUMA-12: Axicabtagene Ciloleucel Shows Substantial Benefit in High-Risk Large B-Cell Lymphoma
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, CAR T-Cell Therapy, Lymphoma
Momelotinib, a Novel JAK Inhibitor, Makes Inroads in Intermediate- or High-Risk Myelofibrosis
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Myelofibrosis, Novel Pharmaceuticals
Oral Vodobatinib Elicits Durable Responses in Heavily Pretreated Patients with Chronic Myeloid Leukemia
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Leukemia, Novel Pharmaceuticals
A Phase 2 Study of Isatuximab for Patients with Previously Treated AL Amyloidosis
Conference Correspondent  published on December 9, 2020 in ASH Highlights
VRD Consolidation Followed by Lenalidomide Maintenance versus Maintenance Alone in Transplant-Eligible Patients with NDMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
A Dose-Finding Study of Belantamab Mafodotin in Combination with Pomalidomide and Dexamethasone for RRMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
Phase 2 GRIFFIN Study Update: Daratumumab + Lenalidomide, Bortezomib, and Dexamethasone in Transplant-Eligible NDMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
Copyright © Green Hill Healthcare Communications, LLC. All rights reserved.